The following discussion is to facilitate the understanding of the invention, but is not intended as reference to prior art.
Diabetes mellitus, often referred to simply as diabetes, is a syndrome of disordered metabolism, usually due to a combination of hereditary and environmental causes, resulting in abnormally high blood glucose level (hyperglycemia). Blood glucose level is controlled by a complex interaction of multiple chemicals and hormones in the body, including the hormone insulin made in the beta cells of the pancreas. Diabetes mellitus refers to the group of diseases that lead to high blood glucose level due to defects in either insulin secretion (Type I diabetes) or insulin action (Type II diabetes). Both Type I and Type II diabetes lead to hyperglycaemia, which largely causes the acute signs of diabetes: excessive urine production, resulting compensatory thirst and increased fluid intake, blurred vision, unexplained weight loss, lethargy, and changes in energy metabolism.
Hyperglycemia may cause long-term microvascular and macrovascular complications, such as nephropathy, neuropathy, retinopathy, and peripheral vascular disease. In addition, diabetes is a comorbid disease that frequently compounds hyperlipidemia, atherosclerosis and hypertension. Hyperlipidemia is a primary risk factor for cardiovascular disease due to atherosclerosis. The long-term complications of diabetes usually are decreased life expectancy, neuropathy, and an increased rate of blindness, kidney disease and heart disease in comparison to nondiabetics.
Diabetes may be controlled with insulin and in some cases through careful diet. However, the blood glucose level will still fluctuate (sometimes dramatically) in patients undergoing insulin or diet therapy. Furthermore, in cases where the diabetes is severe, patients find it necessary to constantly monitor their glucose level to prevent associated illnesses. Diabetic patients are forced to inject insulin which ultimately leads to bruising in certain areas. Furthermore, additional medical complications often arise from diabetes such as arteriosclerosis, hyperlipidemia, retinal damage, neurological damage, fatigue and weakness.
Therefore, there is a need for a safe and effective treatment of diabetes with minimal side effects and/or without the invasive procedures, such as injections.
She chuang zi, also known as Cnidium fruit, fructus cnidii she li, she mi, Taiwan chuan xiong, jia yuan sui and ye hu lo fu zi, is the dried fruit of Cnidium monnieri (L.) Cuss. It has been long used in China as a herb medicine for the treatment of impotence, dampness, infertility, lumbar pain, liking parasites, eczema or vaginal itchiness, itchy skin, trichomoniasis, rectal prolapse, hemorrhoid, and the like. In terms of properties, Cnidium fruit is acrid, bitter and warm. Cnidium monnieri (L.) Cuss. is mainly found in Hebei, Shandong, Zejiang, Jiangsu, Sichuan and Taiwan. The known active ingredients of Cnidium fruit include L-pinene, L-camphene, bornyl isovalarate, isoborneol, osthole, cnidimine (eduotin), cnidiadin, isopimpinelline, xanthotoxol, etc.
Osthole is a coumarin compound, named 7-methoxy-8-isopentenylcoumarin or 7-methoxy-8-(3-methyl-2-butenyl)-2H-1-benzopyran-2-one, which has the following chemical structure:

TW564177B discloses a method for the extraction of osthole from Cnidium fruit, the anti-Tricholmonase vaginalis preparation containing osthole as the main ingredient, and the method of determination of the anti-Trichomonas vaginalis activity of the osthole-containing preparation. Wei, Y., et al., disclose preparative isolation of osthole and xanthotoxol from Common Cnidium Fruit using stepwise elution by high-speed counter-current chromatography (HSCCC) (see J. Chromatogr. A. 2004, 1033(2):373-377). CN101095669A discloses osthole phospholipid complexes, the preparation method thereof and the application, to increase the solubility of osthole.
Recent studies show that osthole has effects on the cardiovascular system, the neural system, the immune system and the metabolism of lipid and bone, such as vascular dilating (see Chiou, W. F., et al., “Vasorelaxing effect of coumarins from Cnidium monnieri on rabbit corpus cavernosum.” Planta. Med. 2001, 67(3):282-284), inhibiting the proliferation of vascular smooth muscle cells (see Guh, J. H., et al., “Antiproliferative effect in rat vascular smooth muscle cells by osthole, isolated from Angelica pubescens.” Eur. J. Pharmacol. 1996, 298(2):191-197), inhibiting the ionic currents in neuronal cells (see Wu, S. N., “Inhibitory effect of the plant-extract osthole on L-type calcium current in NG108-15 neuronal cells.” Biochem. Pharmacol. 2002, 63(2):199-206), anti-allergy (see Matsuda, H., et al., “Anti-allergic effects of cnidii monnieri fructus (dried fruits of Cnidium monnieri) and its major component, osthole.” Biol. Pharm. Bull. 2002, 25(6):809-812), preventing hepatitis (see Okamoto, T., et al., “Osthole prevents anti-Fas antibody-induced hepatitis in mice by affecting the caspase-3-mediated apoptotic pathway.” Biochem. Pharmacol. 2003, 65(4):677-681), inhibiting the growth of tumor cells (see Chou, S. Y., “Antitumor effects of Osthole from Cnidium monnieri: an in vitro and in vivo study.” Phytother. Res. 2007, 21(3):226-230), reducing blood lipid and lowering blood pressure (see Ogawa, H., et al., “Effects of osthol on blood pressure and lipid metabolism in stroke-prone spontaneously hypertensive rats.” J. Ethnopharmacol. 2007, 112(1):26-31), inhibiting alcohol or fatty milk-induced fatty liver (see Sun, F., et al., “Inhibitory effect of osthole on alcohol-induced fatty liver in mice.” Dig. Liver Dis. available online on 11 Mar. 2008; and Zhang, Y., et al., “Therapeutic effect of osthole on hyperlipidemic fatty liver in rats.” Acta Pharmacol. Sin. 2007, 28(3):398-403), and suppressing osteoporosis (see Kuo, P. L., et al., “Osthole-mediated cell differentiation through bone morphogenetic protein-2/p38 and extracellular signal-regulated kinase ½ pathway in human osteoblast cells.” J. Pharmacol. Exp. Ther. 2005, 314(3):1290-1299; Zhang, Q., et al., “Coumarins from Cnidium monnieri and their antiosteoporotic activity.” Planta. Med. 2007, 73(1):13-19; and Li, X. X., et al., “Effects of osthole on postmenopausal osteoporosis using ovariectomized rats; comparison to the effects of estradiol.” Biol. Pharm. Bull. 2002, 25(6):738-742). There is no report of the effect of osthole on the regulation of blood glucose level.